This invention relates to intermediates useful in the preparation of prostaglandin analogs and to a process for preparing them.
Each of the known prostaglandins is a derivative of prostanoic acid which has the following structure and atom numbering: ##STR2## A systematic name for prostanoic acid is 7-[(2.beta.-octyl)cyclopent-1.alpha.-yl]heptanoic acid.
Prostaglandin E.sub.1, "PGE.sub.1 ", has the following structure: ##STR3##
Prostaglandin F.sub.1.alpha., "PGF.sub.1.alpha. ", has the following structure: ##STR4##
The prostaglandin formulas mentioned above each have several centers of asymmetry. Each formula represents a molecule of the particular optically active form of the prostaglandin obtained from certain mammalian tissues, for example, sheep vesicular glands, swine lung, and human seminal plasma, or by reduction or dehydration of a prostaglandin so obtained. See, for example, Bergstrom et al., Pharmacol. Rev. 20, 1 (1968), and reference cited therein. The mirror image of each formula represents a molecule of the other enantiomeric form of that prostaglandin. The racemic form of the prostaglandins consists of equal numbers of two types of molecules, one represented by one of the above formulas and the other represented by the mirror image of that formula. Thus, both formulas are needed to define a racemic prostaglandin. See Nature 212, 38 (1966) for discussion of the stereochemistry of the prostaglandins.
In the formulas above, as well as in the formulas given hereinafter, broken line attachments to the cyclopentane ring indicate substituents in alpha configuration, i.e., below the plane of the cyclopentane ring. Heavy solid line attachments to the cyclopentane ring indicate substituents in beta configuration, i.e., above the plane of the cyclopentane ring. In the formulas above, the hydroxyl attachment to carbon 15 is in the alpha configuration, as indicated by the broken line. In formulas below, this convention is also used for intermediates having hydroxyl substituted at the corresponding position on the side chain. A wavy line .about. indicates attachment to the side chain in alpha or beta configuration.
The various optically active and racemic prostaglandins and their alkyl esters are useful for various pharmacological purposes. With particular regard to PGF.sub.1.alpha. see, for example, Bergstrom et al., Pharmacol. Rev. 20, 1 (1968), and references cited therein. As to the other prostaglandins, see, for example, Ramwell et al., Nature 221, 1251 (1969).
A group of prostaglandin analogs having a divalent phenylene moiety in the carboxyl-terminated side chain of the prostanoic acid structure (I) was disclosed in a pending United States patent application by Norman A. Nelson, Ser. No. 604,158, filed Aug. 13, 1975.
Included among those phenylene prostaglandin analogs were compounds represented by the formulas: ##STR5## wherein Q is ##STR6## and R.sub.1 is hydrogen or alkyl of one to 4 carbon atoms, inclusive.
Previously, certain prostaglandin analogs having an oxa oxygen (-O-) and a divalent phenylene moiety ##STR7## in the carboxyl-terminated side chain of the prostanoic acid structure (I) were disclosed. See U.S. Pat. No. 3,933,898.
Included among those phenylene-oxa prostaglandin analogs were compounds represented by the formulas: ##STR8## wherein Q is as defined above.
Each of the phenylene and phenylene-oxa prostaglandin analogs is useful in place of the corresponding known prostaglandins for at least one of their known pharmacological purposes, which include reduction of gastric secretion, inhibition of blood platelet aggregation, increase of nasal patency, and labor inducement at term.